The acquisition, pathologic characterization and molecular analysis of human and mouse GI tissue samples is a fundamental and integral for all projects of this SPORE application. The Dana-Farber / Harvard Cancer Center (DF/HCC) SPORE in Gastrointestinal (GI) Cancer Tissue and Pathology Core will continue to provide basic and advance pathology services to SPORE investigators in support the studies outlined in each of the Research Projects, as well as in Career Development and Developmental Projects. The Tissue and Pathology Core will collect, store and provide tissue specimens, through interactions with GI Tumor banks and the DF/HCC Pathology Specimen Locator, perform histologic analyses and provide interpretive pathologic analysis of human esophageal, colonic, pancreatic and GI stromal tumors (GISTs). The Core will ensure that appropriately classified GI cancer tissue samples are used and supplied for all immunohistochemical and molecular analyses proposed. In addition, the Core is committed to the characterization of gastrointestinal neoplasms using advanced molecular pathology tools. A variety of services critical to successful molecular analysis of mouse and human GI tumors will be provided, including; histopathologic review and quality control analysis of all tumor samples utilized in experimental studies; construction of tissue micorarrays to improve and streamline all immunohistochemical analyses; selection and macrodlssection of frozen and formalin-fixed, paraffin-embedded (FFPE) tissue samples to ensure that appropriate cellular compartments are utilized in experimental studies; antibody optimizations for applications in immunohistochemistry (IHC); performance and analysis of a broad range of IHC stains in mouse and human tissues in direct support of the projects; and isolation of nuclei acid extractions from all tissue types (fresh frozen and archival FFPE) for molecular analyses. Finally, the Core will evaluate and implement novel technologies such as ex vivo incubation of GI tumor sections and their subsequent molecular characterization in response to treatment, multiplexing of biomarkers and sophisticated cellular imaging techniques.